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Biomedical subjects

S Müller

Publications and source records attributed to S Müller.

At least 433 records · Page 24Linked to original sources

Primary intraosseous squamous carcinoma. Report of two cases.

Two cases of primary intraosseous squamous carcinoma (PIOSC) are reported. One PIOSC is in the mandible of a 24-year-old man and appears to be a keratinizing PIOSC arising de novo. The other PIOSC presented in the edentulous maxilla of a 56-year-old man and was diagnosed as a PIOSC arising from an odontogenic cyst. The 2nd tumor subsequently metastasized to a cervical lymph node. Previous reports have noted a favorable prognosis for PIOC arising in odontogenic cysts, and only 3 other instances of metastases of a PIOSC in an odontogenic cyst have been documented.

Adult↗

Effects of the new class-III antiarrhythmic drug D-sotalol on contractile function of postischemic myocardium.

The hemodynamic effects of the new class-III antiarrhythmic drug D-sotalol (2 mg/kg i.v.) on postischemic myocardium were investigated in comparison with the actions of the racemic D,L-sotalol (2 mg/kg i.v.) in rats. Drug infusion (7 min) was started 20 min after 3 x 4 min of global ischemic injury (oxygen deficiency). The left ventricular isovolumic pressure-generating capacity at the beginning of infusion was reduced by 15%, indicating postischemic dysfunction. Infusion of D-sotalol caused a highly significant (p less than 0.01) reduction of the left ventricular pressure-generating capacity (to 58 +/- 5%), as well as of the dp/dtmax (to 21 +/- 3%). Stroke volume (to 66 +/- 6%), ejection fraction (to 62 +/- 7%), and cardiac output (to 51 +/- 6%) were also decreased (p less than 0.01). Fifteen minutes after infusion a partial renormalization of the hemodynamic measures (dp/dtmax 41 +/- 5%; stroke volume 94 +/- 8%) was observed. Infusion of the racemic D,L-sotalol caused similar hemodynamic changes (left ventricular pressure-generating capacity 60 +/- 2%, dp/dtmax 25 +/- 2%), indicating its cardiodepressant action. In contrast to prior findings on normal myocardium, our present results indicate that D-sotalol, a potential new class-III antiarrhythmic drug, has a considerable negative inotropic effect on postischemic myocardium.

Animals↗

Characterization and molecular cloning of a Cu/Zn superoxide dismutase from the human parasite Onchocerca volvulus.

Evidence suggests that the helminth antioxidant enzyme superoxide dismutase (SOD) may play a role in parasite's defense against the cellular immune mechanisms of the host. In order to investigate this for the human parasite Onchocerca volvulus, the enzyme activity was characterized, the release of SOD by the parasite was examined, and a complete cDNA encoding the O. volvulus SOD was identified. The SOD activity in adult O. volvulus was found to be 8.1 +/- 4.2 U/mg of protein. A Cu/Zn-containing enzyme was demonstrated by its sensitivity towards cyanide, azide, and hydrogen peroxide. Isoelectric focusing, combined with an enzyme activity assay, revealed two activities at pI 6.8 and 7.6, with both activities inhibited by KCN. Adult parasites, maintained in vitro, released SOD into the culture medium, which was detected by enzyme activity. In parallel, lactate production was measured to ensure the viability of the parasite. Oligonucleotides (based upon conserved sequences in the SOD genes of other organisms) and the polymerase chain reaction were used to identify a portion of the SOD gene from O. volvulus genomic DNA. A cDNA library was constructed in lambda unizapII and screened with the genomic polymerase chain reaction fragment. A complete cDNA encoding the Cu/Zn SOD was identified, and its nucleotide sequence was determined. Southern blot hybridization experiments indicated that the Cu/Zn SOD is encoded by a single-copy gene with at least one intron.

Amino Acid Sequence↗

Secretory repertoire of HIV-infected human monocytes/macrophages.

Apart from lymphocytes, mononuclear phagocytes play an essential role as target cells for human immunodeficiency virus (HIV). Circulating blood monocytes (MOs) and tissue macrophages (M phi) may harbor and distribute the virus throughout the body. In addition, proinflammatory monokines [interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)] may contribute to the pathogenesis of HIV-mediated diseases. We have established a culture system on hydrophobic Teflon membranes for blood-borne MOs/M phi. Both freshly isolated MOs as well as MO-derived M phi could be infected with a monocytotropic HIV-1 isolate (HIV-1D117III) derived from a perinatally infected child. The virus production monitored by assay for viral antigen in cell-free supernatant is continuous for several weeks. We analyzed the stimulus response and the secretory repertoire of MOs/M phi early after infection with HIV as well as in long-term cultured, virus-replicating cells. Infected MOs/M phi respond to interferon-gamma more effectively than control cells as estimated from the release of neopterin. The response to lipopolysaccharide was regulated differently: whereas the proinflammatory cytokines IL-1, IL-6, IL-8 and TNF-alpha were up-regulated and even constitutively secreted upon infection, the production of the hematopoietin macrophage-colony-stimulating factor decreased. High levels of TNF-alpha and IL-1 might augment the infectibility of M phi by HIV in an autocrine manner. Our results may provide some explanation for the immunologic dysfunction, the hematopoietic failure and the chronic inflammatory disease occurring in HIV-infected patients.

Biopterins↗

Molecular anatomy of the neuro-immune connection.

Light microscopic immunohistochemistry was employed to elucidate and compare the presence, distribution, and coexistence of various peptides, neuroendocrine markers and enzymes of the catecholamine pathway in nerves supplying lymphoid tissues in a variety of mammalian species. All lymphoid organs and tissues receive innervation by fibers containing dopamine-beta-hydroxylase and/or tyrosine hydroxylase, neural markers like protein gene product 9.5, synaptophysin and neurofilament and a varied spectrum of peptides. The prominent peptides were tachykinins (substance P, neurokinin A), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI). Opioid innervation was variable. Double immunofluorescence revealed coexistence of tachykinins and CGRP and of tyrosine hydroxylase and NPY. A minor proportion of fibers showed coexistence of NPY and tachykinins and of VIP/PHI and tachykinins. The possible importance of the complex peptidergic innervation of lymphoid tissues in inflammation, allergy, inflammatory pain and psycho-neuro-immuno-endocrine network function is discussed. A special immunomodulatory role of the sensory neurons is suggested.

Animals↗

[Tumor scintigraphy using 123I-labeled estradiol in breast cancer--receptor scintigraphy].

The estrogen receptor (ER) status is an important factor for prognosis and endocrine therapy of breast cancer. Therefore 16-alpha-123I-iodoestradiol-17-beta (123I-E2) as a receptor-specific radiopharmacon was used for scintigraphic tumor detection in 62 patients suspected of breast cancer. The studies were performed as a multicenter trial (5 university hospitals) to validate the method and to overcome methodical problems. A fast tracer elimination from the blood pool into the liver was seen, followed by biliary excretion allowing early imaging of the thorax due to low background activity but resulting in difficult imaging conditions of the abdomen. In 42 patients (30 carcinomas, 12 benign lesions) the overall sensitivity was 66% (ER status cut-off: 10 fmol/mg). Some patients with breast cancer showed focal or diffuse uptake in the area of primary lymph drainage (parasternal, axillary) without any clinical correlation, demanding follow-up investigations. There was only one false-positive result in a receptor-negative primary carcinoma; thus, the non-invasive determination of the ER status seems to be feasible. The sensitivity of 123I-E2 in the detection of primary breast cancer or metastases and recurrences is low compared to mammography and other methods; therefore, 123I-E2 scintigraphy cannot be used as a screening method. Differentiation of malignant and benign tissue is even more difficult as both may have a positive ER status, for example in mastopathy. Nevertheless, 123I-E2 scintigraphy is an in vivo imaging technique for the detection of breast cancer depending on the ER status and provides information about tumor localisation. It may become a specific method for the non-invasive diagnosis of the ER status and may be helpful in follow-up studies. As a receptor-specific agent 123I-E2 may give answers to questions of tumor heterogeneity and changes of the ER status during therapy.

Aged↗

Carbon disulfide exposure attenuates adrenergic inotropic response in rats.

Catecholamine-induced myocardial necrosis is enhanced in carbon disulfide exposed rats. We investigated whether the reported morphological findings after carbon disulfide exposure are accompanied by functional disturbances of the adrenergic inotropic response as well as by biochemical alterations. The cardiac effects of epinephrine and norepinephrine were studied in urethane-anesthetized rats which had been subacutely exposed to carbon disulfide. Compared with not exposed control animals left ventricular inotropic response was diminished and the transient T-wave elevation of the ECG due to ischemic episodes was enhanced in carbon disulfide-exposed rats. Activity of LDH-isozymes in the myocardium was shifted toward LDH-M. Our results support the hypothesis that carbon disulfide causes disturbances of energy supply in the heart.

Animals↗

Adrenergic cardiovascular actions in rats as affected by dichloromethane exposure.

Dichloromethane sensitizes the myocardium to arrhythmia development in response to catecholamines. The effects of acute dichloromethane exposure (3.1, 6.2 or 12.4 mmol/kg) on cardiovascular actions of epinephrine (1 or 4 micrograms/kg iv) and norepinephrine (2 or 10 micrograms/kg iv) in the urethane-anaesthetized rat model was investigated. Hypertensive epinephrine effects as well as reflex bradycardia after epinephrine and norepinephrine injections were augmented in dichloromethane-exposed rats. Moreover we observed an enhanced negative dromotropic epinephrine action. The transient T-wave elevation after catecholamine injection was markedly increased in animals treated with 12.4 mmol/kg dichloromethane. The results show that dichloromethane exposure modifies cardiovascular actions after catecholamine administration. The release by dichloromethane of endogenous catecholamines could play a role in the manifestation of these effects.

Adrenergic Fibers↗

Differential occurrence and distribution of galanin in adrenal nerve fibres and medullary cells in rodent and avian species.

The presence and distribution of galanin (GAL) in adrenal glands of rodent and avian species was investigated by light microscopic immunohistochemistry. GAL immunoreactivity was found in all medullary cells of guinea pig, duck and chicken adrenals. In contrast, only a subpopulation of medullary cells stained for GAL in Phodopus (Djungarian hamster) while the neuropeptide was completely missing in chromaffin cells of rat and pigeon. In rat, guinea pig and pigeon, GAL-immunoreactive nerve fibres were frequent in subcapsular regions and sparse in deeper cortical layers and in the chromaffin tissue. In contrast, only very few GAL fibres were found in Phodopus and no GAL fibres were observed in the adrenal glands of duck. In the chicken adrenal gland, fibres containing GAL were numerous throughout the organ and occurred in close vicinity to both steroidogenic as well as catecholaminogenic cells. The striking differences in the presence of GAL-positive cells and fibres are more pronounced between species within the rodent or avian group, respectively, than between the different vertebrate orders. The hitherto unknown and surprising variability of GAL expression and distribution in adrenal glands of various species suggests species-dependent functional (autocrine, paracrine and/or endocrine) roles of GAL in the neuroadrenal axis.

Adrenal Glands↗

[Diagnostic aspects of allergic alveolitis].

The clinical picture of extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis is etiologically extremely multivarious and in disposed persons it can be caused by inhalation of proteins of various species of animals (in particular by avian proteins), mushrooms, bacteria, insects, thermoactinomycetes, vegetable antigens, possibly also haptens after fixation with protein produced inside the body. The inhaled dusts with a size particles of 4 to 5 micrometers which contain the disease-evoking antigens often have an activity-specific character which is expressed in the traditional names of individual forms of alveolitis (e.g. farmer's lung, mushroom-worker's lung, cheese-washer's lung, malt-worker's lung, bagassosis). However, according to our inquiries in the GDR as well as in other parts of Central and East Europe these diseases are relatively rare. In the GDR the so-called bird-fanciers' or bird-keepers' lung with a frequency of 83.4% has a supreme significance within all forms of alveolitis, followed by the farmer's lung (8.9%) and forms of alveolitis by mushrooms (7.7%). In a period of 10 years altogether 7,669 sera of patients with suspicion of alveolitis were investigated at our institute. According to the results of the immunological as well as of further paraclinical and clinical examinations in 550 cases the diagnosis of allergic alveolitis was made (459 bird-fancier's lungs, 49 farmer's lungs and 42 cases of allergic alveolitis by moulds). In 88.5% of the patients who fell ill with extrinsic allergic alveolitis the disease is accompanied by a positive or very positive antigen-specific antibody formation in the blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗

Metabolic chiral inversion of ibuprofen in isolated rat hepatocytes.

Ibuprofen was used to demonstrate that isolated rat hepatocytes offer a suitable in vitro model to investigate the metabolic chiral inversion of anti-inflammatory 2-arylpropionic acids (profens). The inversion of the pharmacologically inactive (-)-(R)-ibuprofen to the active (+)-(S)-ibuprofen was shown to obey apparent first-order kinetics during 5 h and to increase linearly with increasing hepatocyte concentration up to 4 x 10(5) cells/ml. No elimination of (R)-ibuprofen by routes other than inversion was seen, whereas the elimination of (S)-ibuprofen appeared to be saturable.

Animals↗

Numerical analysis of multislice MR excitation and inversion with multifrequency selective rf pulses.

Multifrequency selective excitation and inversion were recently described and tested for multislice imaging and multivolume selective spectroscopy (Magn. Reson. Med. 6, 364 (1988), J. Magn. Reson. 76, 155 (1988]. The technique is based on assumption that a multifrequency rf pulse, a linear superposition of several selective rf pulses with different frequencies, generates a MR signal which can be separated into the spin responses due to each individual frequency. This assumption is investigated theoretically by analyzing the effect of multifrequency selective rf pulses on the magnetization of a homogeneous phantom as a function of slice separation, pulse shape, and rf amplitude using computer simulations of the Bloch equations. It is found that multifrequency selective excitation with sinc pulses--up to eight slices are investigated--and two-frequency inversion with hyperbolic secant pulses lead to profiles comparable in quality and selectivity to those of conventional single-frequency pulses.

Humans↗

Multislice snapshot FLASH using SIMUSIM.

A combination of the SIMUSIM technique and snapshot FLASH which allows efficient multislice snapshot FLASH imaging is described. Simultaneously acquired images of deliberate slice position and thickness are obtained with an increased SNR compared to standard time sequential multislice experiments. Experimental results show four coronal cross sections through the human head measured in four acquisitions.

Brain↗